Professor Greg Goodman AM Dermatologist , adjunct clinical professor , Monash University , Victoria ; honorary professor , University College London , UK .

Images of patients are used with their permission .

Copyright © 2023 Australian Doctor All rights reserved . No part of this publication may be reproduced , distributed or transmitted in any form or by any means without the prior written permission of the publisher . For permission requests , email : howtotreat @ adg . com . au

This information was correct at the time of publication : 2 June 2023

BACKGROUND

TISSUE fillers are used to add

volume or structure to a number of layers of facial and body tissue to help support these tissues . This support may be used to improve appearance , decrease the apparent advance of age or to correct the effects of asymmetry , disease or trauma . There are many tissue fillers , and they may be divided into autologous and non-autologous agents .

Autologous agents are mainly fat , which can be enhanced as a filling agent by using fat-derived stem cells or platelet-rich plasma : a very useful and non-reactive agent . 1-3 Autologous fat remains a very useful agent in cosmetic and reconstructive surgery . Autologous collagen was previously , but is not currently , used . 4

Non-autologous fillers may be permanent or temporary . Permanent fillers have a chequered history , with many — such as silicon and acrylates — prone to complications that are very difficult to treat . 5 Despite this ,

acrylates are still in use , with different brands used in Australia and overseas . 6-9

The temporary non-autologous fillers can be further divided into biostimulatory fillers , which rely on inducing collagen formation after the agent is injected , and non-stimulatory tissue fillers .

Polylactic acid is a classic example of a biostimulatory filler . It has undergone several alterations in dilution techniques , transforming the product from problematic to an acceptable current option . 10 , 11 Calcium hydroxyapatite is a very useful biostimulator , with facial and non-facial uses . 12 , 13 Polycaprolactone is also used for similar purposes . 14

Non-stimulatory tissue fillers have had a long history with collagen — originally , bovine — and then less immunogenic recombinant human equivalents , giving way in the late 1990s to hyaluronic acid ( HA , see figure 1 ). 15

HA initially had many sources ,

including rooster combs or umbilical cords . 16 However , it is largely derived from the coating of a bacterium . 17 Hyaluronic acid is species non-specific ; it is the same repeated disaccharide unit of N-acetyl glucosamine and glucuronic acid no matter where it is sourced .

The possibility of endotoxin load and impurities requires stringent control of the manufacturing processes to ensure a low antigenicity .

Although all HA products are anti-inflammatory in vitro , there is a rate — albeit low — of reactivity to these agents . 18-20 Future changes to HA gels include additives and combination products to allow the deposit of hyaluronic acid to be a source of substances such as antioxidants and

21 , 22 prodrugs , such as tropoelastin .

HA in vivo is produced by fibroblasts but may be created by other cells . It starts its production intracellularly but is too large a molecule to continue being intracellular , so the disaccharide units are exported to

an extracellular docking , where it is joined end to end thousands of times to produce a very large molecule of some 5000KDa or greater .

In humans , HA is present fleetingly in youth in the epidermis but is removed as part of the ageing process . Papillary dermal HA is present throughout life but is dissipated in sun-damaged individuals .

HA acid is not an inert molecule . It has a role as a major component of the dermis , where it helps with the fibres of collagen and elastin to give the dermis the spring and the firmness that underpin the functions of the skin . It is a water-imbibing molecule acting as a sponge in the dermis . However , it is more than this , with innate HA serving many key immunomodulatory functions .

All freshly made innate and injected HA fillers start out as high molecular – weight HA ( HMWHA , see figure 2 ). This is a signalling molecule and interacts with the immune system through its receptors ( clustered